Mimetics of sulfated oligosaccharides

Abstract

The present invention is directed to sulfated oligosaccharides having 4, 5 or 6 saccharidic units and wherein a glycosidic bond between two saccharide units is substituted by a C—C bond, and wherein the sulfation degree expressed as percentage of OH groups substituted by a OSO 3 − group is comprised between 50 and 100%. The sulfated oligosaccharides according to the invention are useful as a drug, in particular in the treatment of angiogenesis, metastasis, and inflammation.

The invention claimed is: 
     
       1. Sulfated oligosaccharides wherein a glycosidic bond between two saccharide units is substituted by a C—C bond, wherein the C—C bond is between the positions 1-1, 2-2, 5-5 or 6-6, and wherein the sulfation degree, expressed as percentage of OH groups substituted by a OSO 3   −  group, is between 50 and 100%. 
     
     
       2. Sulfated oligosaccharides according to  claim 1  wherein the oligosaccharide has 4, 5 or 6 saccharide units. 
     
     
       3. Sulfated oligosaccharides according to  claim 2  wherein the bond is between the positions 1,1 and the conformation is α-α, α-β or β-β. 
     
     
       4. Sulfated oligosaccharides according to  claim 1 , wherein the compound is expressed by the formula: 
       
         
           
           
               
               
           
         
       
       wherein X can be OH, OSO 3   −  or an optionally sulfated saccharide or oligosaccharide group; Y is selected from the group consisting of CH 2 OH, CH 2 OSO 3   − , COOH, COOR wherein R is selected from the group consisting of alkyl, aryl, acyl, aroyl, alkyl sulfonyl, aryl sulfonyl, PEG. 
     
     
       5. Sulfated oligosaccharides according to  claim 1 , wherein the compound is expressed by the formula: 
       
         
           
           
               
               
           
         
       
       wherein X can be OH, OSO 3   −  or an optionally sulfated saccharide or oligosaccharide group; Y is selected from the group consisting of CH 2 OH, CH 2 OSO 3   − , COOH, COOR wherein R is selected from the group consisting of alkyl, aryl, acyl, aroyl, alkyl sulfonyl, aryl sulfonyl, PEG; G is OH, OSO 3   − , OR wherein R is selected from the group consisting of alkyl, aryl, acyl, aroyl, alkyl sulfonyl, aryl sulfonyl, PEG, or an optionally sulfated saccharide or oligosaccharide group; Z is OH, OSO 3   −  or an optionally sulfated saccharide or oligosaccharide group. 
     
     
       6. Sulfated oligosaccharides according to  claim 1  wherein the oligosaccharide is an hexasaccharide and the C—C bond is between the third and fourth unit. 
     
     
       7. A method of treatment of angiogenesis comprising administering to a mammalian in need of such treatment an effective amount of a compound of  claim 1 . 
     
     
       8. A method of treatment of metastasis comprising administering to a mammalian in need of such treatment an effective amount of a compound of  claim 1 . 
     
     
       9. The method of  claim 7  wherein the compound has a sulfation degree between 60 and 100%. 
     
     
       10. A method of treatment of inflammation comprising administering to a mammalian in need of such treatment an effective amount of a compound of  claim 1 . 
     
     
       11. The method of  claim 10  wherein the compound has a sulfation degree between 80 and 100%.